(New York, NY – May 8, 2006) Results from a Cancer Research Institute (CRI) funded study at Wake Forest University School of Medicine show that resistance to highly aggressive cancers can be transferred from a strain of cancer-resistant mice into ordinary mice, causing complete destruction of large tumors and life-long protection against future tumor challenges. This resistance is based on innate immunity to cancer rather than adaptive immunity based on T and B cells. In an effort to accelerate the translation of this discovery into a potential cancer therapy for humans, the Cancer Research Institute has established a unique collaboration with four other major U.S. research institutions that will work together to unlock the molecular and genetic mysteries behind this mouse's remarkable immunity.
“The amazing thing is that these cancer resistant mice are innately immune to very aggressive cancers that are injected in amounts that would kill just about any other animal,” said Jill O'Donnell-Tormey, Ph.D., CRI's executive director. “It is a highly unusual phenomenon, but one that strongly suggests something is going on inside these mice that merits further expert investigation.”
According to Zheng Cui, M.D., Ph.D., associate professor of pathology at the Wake Forest University School of Medicine and primary author of the study published in the May 8, 2006, issue of The Proceedings of the National Academy of Sciences (PNAS), the immunity is caused by a genetic mutation. “The most critical challenges now,” he said, “are to locate the gene mutation that is causing this immunity and to find out what's going on at the molecular level. If we can do this, then we can begin to understand what, specifically, makes these mice different from other mice.”
To help Dr. Cui accomplish this task, the Cancer Research Institute has brokered a collaboration that teams Cui's laboratory with those of Bruce Beutler, M.D., an immunogeneticist at the Scripps Research Institute in La Jolla, CA, Robert D. Schreiber, Ph.D., a molecular immunopathologist at the Washington University School of Medicine in St. Louis, MO, and Pramod K. Srivastava, Ph.D., an immunobiologist at the University of Connecticut Health Science Center in Farmington, CT.
Among their many accomplishments, Dr. Beutler is credited with co-discovering which genes allow the mammalian innate immune system to recognize dangerous microbial infections, Dr. Schreiber has proven that the immune system recognizes and destroys cancer cells in healthy animals, and Dr. Srivastava has discovered the role of heat-shock proteins in immunity to cancer and infectious diseases. With one of the world's largest mutagenesis studies under his supervision, Dr. Beutler will attempt to locate the genetic mutation responsible for the mouse immunity. Meanwhile, Dr. Schreiber will use his new human-like mouse cancer models to further characterize the extent of the mouse immunity, especially its ability to defend against cancers that arise within the mice themselves versus cancers that are transplanted. In his laboratory in Connecticut, Dr. Srivastava will attempt to locate the molecular factor(s) produced by the tumor cells that elicit the anti-tumor response.
“There are many challenges to advancing a discovery like Dr. Cui's into a therapy for humans,” Dr. O'Donnell-Tormey said. “It requires the involvement of individuals with many different areas of expertise. No one person can do it alone; work of this complex nature demands collaboration.” CRI understands collaboration. In 2001, CRI joined with the Ludwig Institute for Cancer Research to launch their Cancer Vaccine Collaborative (CVC) and Cancer Antigen Discovery Collaborative (CADC) programs. Like the Cui mouse collaboration, the CVC and CADC bring together experts from diverse fields who work collectively on shared goals. These programs provide a centralized matrix through which participants freely exchange data and reagents from parallel, single-variable studies.
“Collaborations like these don't just happen. They have to be encouraged,” said Dr. O'Donnell-Tormey. Dr. Lloyd J. Old, director of CRI's Scientific Advisory Council and Chairman of the Ludwig Institute, has been the motivating force behind forming the Cui collaboration. “These studies have revealed an unexpectedly powerful feature of cancer immunity,” Dr. Old said. “The magnitude and rapidity of the antitumor response are unprecedented. If the collaborative enterprise CRI has put in defines the gene and molecules involved in this remarkable phenomenon, we can then look for the comparable system in humans. That would open up a world of therapeutic possibilities,” he said. “Our goal is to help accomplish this in as short a time as possible.”